WO2024003946A1 - Poly-herbal composition for respiratory illnesses - Google Patents

Poly-herbal composition for respiratory illnesses Download PDF

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WO2024003946A1
WO2024003946A1 PCT/IN2023/050636 IN2023050636W WO2024003946A1 WO 2024003946 A1 WO2024003946 A1 WO 2024003946A1 IN 2023050636 W IN2023050636 W IN 2023050636W WO 2024003946 A1 WO2024003946 A1 WO 2024003946A1
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composition
amount
extract
poly
herbal composition
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PCT/IN2023/050636
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French (fr)
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Sankarasubramanian Lakshmisubramanian
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Swasti Veda Private Limited
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/32—Burseraceae (Frankincense family)
    • A61K36/324—Boswellia, e.g. frankincense
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/59—Menispermaceae (Moonseed family), e.g. hyperbaena or coralbead
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9064—Amomum, e.g. round cardamom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • Airway inflammation is caused by allergens that include non-living materials such as dust, chemical vapours, and pollens and living organisms that include bacteria, spores, viruses etc. This inflammation triggers various immune responses in humans that include release of histamines from specialized immune cells. These histamines when flushing out the non-living allergens cause enlargement of cells in the bronchial tube which makes breathing difficult.
  • the innate immune response recognizes pathogen-associated molecular patterns activating several defence cells. These cells produce inflammatory compounds called cytokines, while acting on the infectious pathogen and then present it to the antigen-specific adaptive immune system containing T-cells and B-cells. Inflammation is a double-edged sword. Controlled and modest pro-inflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled pro-inflammatory responses may increase the susceptibility to colonization infections that facilitate disease pathogenesis and pathophysiological effects.
  • the PCT Application W02020208659 discloses an anti-viral, anti-bacterial, immuno-boosting single composition for respiratory tract infections consisting of standardized alcoholic extracts of the herbs, combined together in specific synergistic ratios as - Curcuma longa (95% Curcumin) 26-31%; Boswellia serrata resin (65% Boswellic acid)- 22-27% ⁇ Vforz «ga pterygosperma (leaves) - 18-23%; Ocimum sanctum (leaves) -7-12%; Tinospora cordifolia (stem) - 7-12%; Withania somnifera (leaves)- 5-7%; Piper nigrum fruit (95% Piperine)- 1-2%.
  • the Indian Patent Application no. 201621037854 discloses a polyherbal composition for boosting overall immunity which comprises an extract of Emblica officinalis in the range of 3 wt% to 5 wt% of the total weight of the composition; together with other plant extracts selected from the group consisting of Aegle marmelos, Piper longum, Tribulus terrestris, Vitis vinifera, Leptadenia reticulata, Inula racemosa, Tinospora cordifolia, Sida cordifolia, Curcuma zedoaria, Cyperus rotundus, Boerhaviadiffusa, Amomum subulatum, Adhatoda zeylanica, Withania somnifera, Cinnamomum zeylanicum, Elettaria cardamomum, Cinnamomum tamala, and Syzygium aromaticum.
  • a further objective is to provide a process of standardizing the extracts of the herbs/plant used in the present invention and formulating into desired compositions.
  • the present invention provides poly herbal composition with immune-modulating activity effective against various respiratory diseases/ailments associated with inflammation, impaired lung function, fatigue, breathlessness etc. comprising the standardized extracts of Acacia arabica, Achyranthes aspera, Adhatoda vasica, Boswellia serrata, Camellia sinensis, Plumbago zeylanica, Solanum xanthocarpum, Tinospora cordifolia, Withania somnifera, Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinale in suitable proportions.
  • the present invention provides a process for preparing the extracts of the above herbs/plants from the plant parts.
  • the extractions can be carried out through aqueous solvent or any other organic solvent depending on the active compounds in the individual plant materials, and are not restricted to ethanol, methanol, ethyl acetate, acetone, ethylene chloride and the like, as per the need of the extractable active compounds from individual plant materials.
  • the present invention provides a method for preparing the poly- herbal composition comprising blending the aqueous, alcoholic, or organic solvent extracts of Acacia arabica, Achyranthes aspera, Adhatoda vasica, Boswellia serrata, Camellia sinensis, Plumbago zeylanica, Solanum xanthocarpum, Tinospora cordifolia, Withania somnifera, Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinalem suitable proportions along with applicable additive s/excipients.
  • the poly-herbal composition may further contain acceptable additives/excipients such as binders, sweetening agents, preservatives, permitted fdlers, colouring agents, flavouring agents, lubricants, disintegrating agent, moisture absorbents and the like and may be formulated in solid or liquid form such as dry powder, tablets, capsules, pills, syrup, suspensions and the like.
  • acceptable additives/excipients such as binders, sweetening agents, preservatives, permitted fdlers, colouring agents, flavouring agents, lubricants, disintegrating agent, moisture absorbents and the like and may be formulated in solid or liquid form such as dry powder, tablets, capsules, pills, syrup, suspensions and the like.
  • the present invention provides a method for treating the bronchial hyperresponsiveness of the lungs when exposed to living and non-living allergens, to relieve fatigue and improving lung function comprising providing an effective amount of the present poly-herbal composition to the subject in need thereof.
  • the poly-herbal composition of the present invention is effective in treating the hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs.
  • Fig 1 Depicts(a) graph indicating the the variation of D-Dimer values in some of the patients before and after treatment with said poly-herbal composition; (b) The bars indicating a decrease in D-Dimer levels.
  • Fig 2 Depicts (a) Variations in CRP values among the infected patients;(b) bars indicating a decrease in C-Reactive Protein levels after consuming the present poly-herbal composition, restoringnormalcy in patients after 5 days.
  • Fig 3 Depicts the bars indicating a decrease in IL-6 levels after consuming poly- herbal composition, restoring to normalcylevels of ( ⁇ 7pg/ml).
  • Achyranthes aspera o Source This plant is procured from India. o Geographical Origin: Throughout the tropical world
  • Boswellia serrata o Source This plant is procured from India as well as from abroad. Geographical Origin: Native to much of India and the Punjab region that extends into Pakistan.
  • Camellia sinensis o Source The plant is procured from India.
  • o Geographical Origin Native to East Asia, the Indian Subcontinent, and Southeast Asia.
  • Cinnamomum zeylanicum o Source The plant is procured from Sri Lanka. o Geographical origin :Native to Sri Lanka.
  • Nigella sativa o Source The plant is procured from India. o Geographical origin: Native to a large region of the eastern Mediterranean, northern Africa, the Indian subcontinent, and West Asia.
  • Piper nigrum o Source The plant is procured from India. o Geographical origin: Native to present-day South India and is extensively cultivated in tropical regions.Vietnam is the largest producer and exporter of pepper.
  • Plumbago zeylanica o Source The plant is procured from India and Sri Lanka. o Geographical origin:Native to Southeast Asia, Indonesia, the Philippines, and Yunnan in southern China.
  • Solanum xanthocarpum o Source The plant is procured from India. o Geographical origin: This plant is cultivated in Himalayas, South- East Malaysia, Australia, and Polynesia region.
  • Tinospora cordifolia o Source The plant is procured from India. o Geographical origin: indigenous to tropical regions of the Indian subcontinent.
  • the present invention relates to a poly-herbal composition
  • a poly-herbal composition comprising; a) an extract of Acacia arabica bark in an amount of 15-30% w/w of the composition; b) an extract of Achyranthes aspera root in an amount of 19-28%w/w of the composition; c) an extract of Adhatoda vasica leaf in an amount of 24-27%w/wof the composition; d) an extract of Boswellia serratarcsin in an amount of 25-30%w/w of the composition; e) an extract of Camellia sinensis leaf in an amount of 10-18%w/w of the composition; f) an extract of Cinnamomum zeylanicum bark in an amount of 15-25%w/w of the composition; g) an extract of Curcuma longa rhizome in an amount of 15-18%w/w of the composition; h) an extract of Elettaria cardamomum fruit in an amount of 12-14%w
  • the poly-herbal composition of the present invention may contain the additive s/excipients selected from permitted fillers, stabilizer, lubricants, preservative, moisture absorbents, binders, disintegrating agents, colouring agents, flavouring agents in suitable amounts depending on solid and liquid dosage forms.
  • the parts of the herbs/plants used in said composition are: a) Acacia arabica: Bark b) Achyranthes aspera: Root and seed c) Adhatoda vasica: Leaves d) Boswellia serrata: Resin e) Camellia sinensis: Green leaves f) Cinnamomum zeylanicum: Bark g) Curcuma longa: Rhizome h) Elettaria cardamomum: Fruit i) Nigella sativa: Seed j) Piper longum: Fruit k) Piper nigrum: Fruit l) Plumbago zeylanica: Root m) Solanum xanthocarpum: Fruit n) Syzygium aromaticum: Bud o) Tinospora cordifolia: Aerial portion p) Withania somnifera: Rhizome q) Zingiber officinale: Rhizome
  • the present invention discloses the process for preparation of said poly-herbal composition
  • said process for preparation of said poly-herbal composition comprising; i. Extracting the plant materials of Acacia arabica, Achyranthes aspera, Adhatoda vasica, Boswellia serrata, Camellia sinensis, Plumbago zeylanica, Solanum xanthocarpum, Tinospora cordifolia, Withania somnifera collectively or individually with water in the ratio of 1:4 to 1:8 followed by subjecting to a hydroalcoholic extraction in the ratio between 1:2 and 1:6 and standardizing the phytoconstituents to 30-40% solids by concentration, followed by spray drying to uniformity; ii. Individually extracting 50% percent of the amount of
  • the bark of Acacia arabica, the seeds of Achyranthes aspera, the leaves of Adhatoda vasica, the resin of Boswellia serrata, the green leaves of Camellia sinensis, the root of Plumbago zeylanica, the fruit of Solanum xanthocarpum, the aerial portion of Tinospora cordifolia, the rhizome of Withania somnifera are subjected to extraction collectively or individually with water in the ratio of 1:4 to 1:8.
  • hydro-alcoholic mixture in the ratio between 1:2 and 1:6 wherein the important phytoconstituents such as alkaloids, flavonoids, glycosides and saponins, and active compounds such as catechins, tannic acid, vasicine, withanolide, piperine, curcuminoids, eugenol and gingerols,are extracted and standardizedto 30-40% solids by concentration, followed by spray drying to uniformity.
  • important phytoconstituents such as alkaloids, flavonoids, glycosides and saponins
  • active compounds such as catechins, tannic acid, vasicine, withanolide, piperine, curcuminoids, eugenol and gingerols
  • step (ii) 50% of the total plant material of the bark of Cinnamomum zeylanicum, the rhizome of Curcuma longa, the fruit of Elettaria cardamomum, the seed of Nigella sativa, the fruit of Piper longum, the fruit of Piper nigrum, the bud of Syzygium aromaticum and the rhizome of Zingiber officinale are subjected to individual extraction with suitable solvents which are standardized to the active oleoresins or its analogues derived from said plants followed by stripping off the solvent from the extract.
  • the standardized oleoresins obtained were then encapsulated with the natural polymer, gum acacia, for further formulation processing.
  • the remaining 50% of the total plant material of the bark of Cinnamomum zeylanicum, the rhizome of Curcuma longa, the fruit of Elettaria cardamomum, the seed of Nigella sativa, the fruit of Piper longum, the fruit of Piper nigrum, the bud of Syzygium aromaticum and the rhizome of Zingiber officinale are subjected to hydro-alcoholic extraction and collectively spray dried.
  • All the spray dried extracts and encapsulated extracts were blended to homogeneity and granulated (to avoid addition of preservatives) or used as such along with permitted fdlers, preservatives, moisture absorbents, stabilizers, lubricants, binders colouring agents, flavouring agents and such acceptable inactive compounds to formulate the desired composition.
  • the extractions may be carried out through aqueous solvent or organic solvent, not restricted to ethanol, methanol, ethyl acetate, acetone, ethylene chloride or as per the need of the extractable active compounds from individual plant materials.
  • the poly-herbal composition of the present invention may be formulated as nutraceutical composition in solid or liquid form such as dry powder, tablets, capsules, pills, soft gel capsule, lozenges, syrups, suspensions and the like.
  • the poly-herbal composition is formulated as capsules which contain the standardized extracts of the plants/herbs at dosages of 260-400mg per capsule.
  • the dosage of the standardized extracts of the plants/herbs in tablets or in lozenges, as powders, pills, syrups, suspensions and the like depend on a number of factors including whether the extracts of the plants/herbs as active is to be administered for therapeutic use, the type of viral infection, the severity of the condition, the age of the individual, and related factors including weight and general health of the individual as may be determined in accordance with accepted medical principles.
  • frequency of administration of the poly-herbal composition can be determined by continuously monitoring the individual's response between each dosage and if necessary, increasing the frequency of administration or alternatively, reducing the frequency of administration.
  • the poly-herbal composition of the present invention exhibits immune -modulator activity and can be used for treating the bronchial hyper responsiveness of the lungs when exposed to living and non-living allergens, to relieve fatigue and improving lung function.
  • the poly-herbal composition of the present invention is effective in treating the hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs.
  • the present invention discloses a method treating the hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs comprising providing the poly-herbal composition to a subject in need thereof.
  • the present poly-herbal composition addresses the problems related to various respiratory ailments/diseases caused due to living and non-living allergens by controlling and reducing the parameters such as CRP, ESR, IL-6, D-Dimer, LDH and co-morbid conditions which are critical for treating the bronchial hyper responsiveness of the lungs, to relieve fatigue and improving lung function.
  • the poly-herbal composition of the present invention is useful for regulating the expression of cytokines from triggered immune cells thereby controlling the extraordinary response, repairing the lungs and helping restore lung function.
  • Example 1 Poly-herbal Composition
  • Example 2 Process for the preparation of poly-herbal Composition
  • Cinnamomum zeylanicum(15 kg) was extracted using acetone for 12hrs at 40°C.
  • the rhizome of Curcuma longa(2() kg) was extracted using the solvent mixture of ethyl acetate and hexane for 12hrs at 60°C.
  • the fruit of Elettaria cardamomum (1 kg) was extracted by steam distillation (100°C) for extracting oil and in ethyl acetate for 12hrs at 40°C.
  • the seed of Nigella sativa(25 ⁇ sg) was subjected to supercritical fluid extraction for 8hrs at 30°C.
  • the fruit of Piper longum( ⁇ 5 kg) was extracted using the solvent mixture of acetone and ethyl acetate for 12hrs at 60°C.
  • the fruit of Piper nigrum (37.5 kg) was extracted using ethyl acetate for 12hrs at 60°C.
  • the bud of Syzygium aromaticum (30 kg) was extracted using the solvent mixture of ethyl acetate and hexane for 12hrs at 40°C.
  • the rhizome of Zingiber officinale( Q kg) was extracted using the solvent mixture of ethyl acetate and acetone for 12hrs at 40°C.
  • the extracts were standardized to 6-7% of active oleoresins or its analogues derived from said plants followed by stripping off the solvent under vacuum from the extract.
  • the standardized oleoresins so obtained were then encapsulated with the natural polymer, gum acacia for further formulation process.
  • step (iv) All the spray dried extracts of step (i) and (iii) and encapsulated extracts of step (ii) were blended to homogeneity, added permitted fdlers, preservatives, moisture absorbents and pharmaceutically inactive compounds to formulate the desired composition in solid and liquid forms.
  • the fine blend of the standardized extracts of example 3 was filled into capsules to give oral dosage of 2 capsules of approximately400 mg each, i.e., 2-0-2 for treatment of patients suffering from respiratory illnesses and who were positive to viral RNA with or without lung involvement as measured through HRCT (High- resolution computed tomography) scan.
  • HRCT High- resolution computed tomography
  • a total of 43 volunteers (both male and female) were enrolled.
  • the parameters studied include complete blood cell counts, Liver Function tests, Kidney function tests, HRCT scan, IL-6, LDH, D-Dimer, CRP and external symptoms such as cough, fever, respiration rate and oxygen requirements.
  • the volunteers were classified into mild and moderately affected based on their lung involvement and blood markers such as IL-6, LDH, D-Dimer and CRP.
  • the volunteers’ data was further classified on the basis of age, co-morbidities, abnormal levels of blood parameters, and symptoms such as cough, fever and oxygen requirement etc. and analyzed. Results:
  • Moderately affected patients had abnormal values of a few blood cell counts, such as RBC, leucocytes (WBC), platelets, neutrophils, eosinophils and lymphocytes, along with enhanced values of CRP, IL-6, D-Dimer, LDH and Ferritin. Mild patients had less than 5% of lung involvement of the disease whereas moderately affected patients had up to 45% of lung involvement with respect to their HRCT images.
  • D-dimer is a protein fragment (small piece) that is made when a blood clot dissolves in the body.
  • a decrease in D-Dimer levels was observed after taking the poly-herbal composition of the present invention thereby restoring normalcy.
  • the D-Dimer levels in the volunteers were higher than the normal maximum limit.
  • the D-Dimer levels tapered off until they were within the acceptable range (Figs. 1(a) and (b)).
  • CRP C-Reactive protein
  • a CRP test measures the amount of CRP in the blood, to detect inflammation due to acute conditions or to monitor the severity of disease in chronic conditions.
  • a decrease in C - reactive protein levels after taking the poly-herbal composition was observed, restoring normalcy in volunteers after 5 days. In the initial stage the CRP levels in the volunteers were higher than the normal range. Increase in CRP levels can be attributed to the progression of the disease (Figs 2(a) and (b)).
  • Interleukin-6 seems to be associated with an inflammatory response, respiratory failure, need for mechanical ventilation and/or intubation, and mortality. Volunteers with the highest levels of complications exhibited 3 or more times higher levels ofIL-6 than noncomplicated volunteers. IL-6 is predictive of progression in severity of the disease and in-hospital mortality. A decrease in IL-6 levels after taking the poly herbal composition was observed, restoring to normalcy levels of ⁇ 7pg/ml (Fig 3).
  • a decreased leukocyte count (less than 4000 cells/mm) in the early stages of infection of the virus and from 3rd day after the consumption of poly-herbal composition was noted.
  • the volunteers showed increased counts (indicative of an increased response to the virus) and with a maximum value between 6500 and 7280 cells(average) on the 5th day (Fig 4).
  • PEFR(Peak expiratory flow) is a person's maximum speed of expiration, as measured with a peak flow meter.
  • Piper nigrum and Piper longum, Curcuma longa,Achyranthes aspera, Syzygium aromaticum, Acacia arabica, Zingiber officinale, Adhatoda vasica, Solanum xanthocarpum, Elettaria cardamomum are known to have different functions such as protease inhibitor(anti-viral), antiinflammatory, IL-6 blocker, prostaglandin biosynthesis inhibitor, reduction of bronchial mucosal oedema, individually or in combination, the present poly herbal composition provides total relief from all the symptoms in short time as shown above.
  • the poly-herbal composition is safe without any side effects with the potential to overcome the limitations of the present synthetic drugs available in the market.

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Abstract

Disclosed herein is a poly-herbal composition/formulation for the treatment of respiratory ailments or illnesses associated with inflammation, impaired lung function and fatigue and to the process of preparation thereof. The present invention provides a safe and effective solution to the limitations of the marketed synthetic drugs used for respiratory ailments or illnesses.

Description

POLY-HERBAL COMPOSITION FOR RESPIRATORY ILLNESSES
FIELD OF THE INVENTION
The present invention relates to a poly-herbal formulation for treatment of illnesses or ailments of the human respiratory system associated with inflammation, impaired lung function and fatigue and to the process of preparation thereof.
BACKGROUND OF THE INVENTION
Airway inflammation is caused by allergens that include non-living materials such as dust, chemical vapours, and pollens and living organisms that include bacteria, spores, viruses etc. This inflammation triggers various immune responses in humans that include release of histamines from specialized immune cells. These histamines when flushing out the non-living allergens cause enlargement of cells in the bronchial tube which makes breathing difficult.
Bronchial hyperresponsiveness is known to occur during acute airway inflammation and there is involvement of an augmented reflex broncho constriction in these pathophysiological conditions. A higher level of inhaled irritant will generate a greater intensity of afferent discharge during airway inflammation, which consequently causes a more severe broncho constriction in the bronchial tube leading to airway dysfunction.
Entry of infectious pathogens into the human respiratory system either directly through the nasal route or indirectly through the mouth or other organs, gives two types of responses - an innate and adaptive immune response.
The innate immune response recognizes pathogen-associated molecular patterns activating several defence cells. These cells produce inflammatory compounds called cytokines, while acting on the infectious pathogen and then present it to the antigen-specific adaptive immune system containing T-cells and B-cells. Inflammation is a double-edged sword. Controlled and modest pro-inflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled pro-inflammatory responses may increase the susceptibility to colonization infections that facilitate disease pathogenesis and pathophysiological effects.
Repeated exposure of living and non-living substances to immune system elicits hyper inflammation and this inflammation response is higher when infected with viruses and bacteria because they multiply very fast. Viral pathogenesis causes hijacking of the host cells and its components for survival and multiplication, and hence hyper-inflammation is severe in the case of viral infections.
Fatigue is an incapacitating symptom and a leading cause of consultations in chronic respiratory illnesses, but is poorly understood, under diagnosed, and under treated. There are two types of fatigue, performance and perceived, both controlled by different factors acting at a micro and macro level. Both types of fatigue can exert a negative influence on motor, cognitive and psychosocial functioning. Severe fatigue is the result of oxygen deprivation and can lead to brain hypoxia and/or respiratory failure.
In the past few decades there has been exponential growth in the field of herbal medicines for both viral and bacterial infections, exploring the variety of herbs/plants with immune-boosting activity, producing maximum benefits for the treatment of various respiratory diseases.
The PCT Application W02020208659 discloses an anti-viral, anti-bacterial, immuno-boosting single composition for respiratory tract infections consisting of standardized alcoholic extracts of the herbs, combined together in specific synergistic ratios as - Curcuma longa (95% Curcumin) 26-31%; Boswellia serrata resin (65% Boswellic acid)- 22-27%^Vforz«ga pterygosperma (leaves) - 18-23%; Ocimum sanctum (leaves) -7-12%; Tinospora cordifolia (stem) - 7-12%; Withania somnifera (leaves)- 5-7%; Piper nigrum fruit (95% Piperine)- 1-2%.
WO03055558 discloses an herbal composition for bronchial asthma comprising Achyranthes aspera'. 15.5%-17. 5%; Woodfordiafruticosa'. \ \ .5%- \ 3.6%: Solanum xanthocarpum 11.5 % - 13. 6 %; Justicia adhatoda 11. 5 %-13.6 %; Acacia arabica 11. 5 %-13. 6 %; Zingiber officinale'. 3.6 % - 4. 94%; Syzygium aromaticum bud: 3.6 %-4.94 %; Curcuma longa'. 3.6 - 4.94%; Holarrhenaantidysenterica'. 3.6 % -4. 94 %; Enicostemma littoralc. 2.22%-3.3%; Calotropis procera'. 2.22%-3.3%; Piper longunr. 2. 22 %-3.3 %; Piper nigrum'. 8. 2 %-7. 8 %; Elettaria cardamomum'. 0. 06 %-0. 19 %.
The Indian Patent Application no. 201621037854 discloses a polyherbal composition for boosting overall immunity which comprises an extract of Emblica officinalis in the range of 3 wt% to 5 wt% of the total weight of the composition; together with other plant extracts selected from the group consisting of Aegle marmelos, Piper longum, Tribulus terrestris, Vitis vinifera, Leptadenia reticulata, Inula racemosa, Tinospora cordifolia, Sida cordifolia, Curcuma zedoaria, Cyperus rotundus, Boerhaviadiffusa, Amomum subulatum, Adhatoda zeylanica, Withania somnifera, Cinnamomum zeylanicum, Elettaria cardamomum, Cinnamomum tamala, and Syzygium aromaticum.
Several complications that include multisystem inflammatory syndrome, pneumonia, acute respiratory distress syndrome, chronic cough, septic shock, blood clots, arrhythmia, secondary infections, injury to kidney, liver etc. are associated with many infectious agents.
Further, considering the increasing resistance to existing drug molecules for many emerging and re-emerging viral diseases, the present inventors felt that there remains a scope in the art to provide immune-modulatingpoly-herbal composition/ formulation for the treatment of various respiratory illnesses associated with inflammation, fatigue, myalgia, breathlessness etc.
OBJECTIVE OF THE INVENTION
It is the primary objective of the present invention to provide poly-herbal composition/formulation for treatment of respiratory diseases associated with inflammation, fatigue, myalgia, breathlessness etc.
A further objective is to provide a process of standardizing the extracts of the herbs/plant used in the present invention and formulating into desired compositions.
SUMMARY OF THE INVENTION
In accordance with the above, the present invention provides poly herbal composition with immune-modulating activity effective against various respiratory diseases/ailments associated with inflammation, impaired lung function, fatigue, breathlessness etc. comprising the standardized extracts of Acacia arabica, Achyranthes aspera, Adhatoda vasica, Boswellia serrata, Camellia sinensis, Plumbago zeylanica, Solanum xanthocarpum, Tinospora cordifolia, Withania somnifera, Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinale in suitable proportions.
In another aspect, the present invention provides a process for preparing the extracts of the above herbs/plants from the plant parts. The extractions can be carried out through aqueous solvent or any other organic solvent depending on the active compounds in the individual plant materials, and are not restricted to ethanol, methanol, ethyl acetate, acetone, ethylene chloride and the like, as per the need of the extractable active compounds from individual plant materials.
In another aspect, the present invention provides a method for preparing the poly- herbal composition comprising blending the aqueous, alcoholic, or organic solvent extracts of Acacia arabica, Achyranthes aspera, Adhatoda vasica, Boswellia serrata, Camellia sinensis, Plumbago zeylanica, Solanum xanthocarpum, Tinospora cordifolia, Withania somnifera, Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinalem suitable proportions along with applicable additive s/excipients.
The poly-herbal composition may further contain acceptable additives/excipients such as binders, sweetening agents, preservatives, permitted fdlers, colouring agents, flavouring agents, lubricants, disintegrating agent, moisture absorbents and the like and may be formulated in solid or liquid form such as dry powder, tablets, capsules, pills, syrup, suspensions and the like.
In an aspect, the present invention provides a method for treating the bronchial hyperresponsiveness of the lungs when exposed to living and non-living allergens, to relieve fatigue and improving lung function comprising providing an effective amount of the present poly-herbal composition to the subject in need thereof.
In another aspect, the poly-herbal composition of the present invention is effective in treating the hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs.
DESCRIPTION OF THE FIGURES
Fig 1: Depicts(a) graph indicating the the variation of D-Dimer values in some of the patients before and after treatment with said poly-herbal composition; (b) The bars indicating a decrease in D-Dimer levels.
Fig 2: Depicts (a) Variations in CRP values among the infected patients;(b) bars indicating a decrease in C-Reactive Protein levels after consuming the present poly-herbal composition, restoringnormalcy in patients after 5 days.
Fig 3: Depicts the bars indicating a decrease in IL-6 levels after consuming poly- herbal composition, restoring to normalcylevels of (<7pg/ml). DETAILED DESCRIPTION OF THE INVENTION
The present invention will now be explained in detail with reference to its various preferred as well as optional embodiment, which, should not be construed to limit the scope of the invention.
Source and Geographical Origin of the herbs used in the present invention:
• Acacia arabica o Source: This plant is procured from India. o Geographical Origin: Native to Africa, the Middle East and the Indian subcontinent.
• Achyranthes aspera o Source: This plant is procured from India. o Geographical Origin: Throughout the tropical world
• Adhatodavasica o Source: This plant is procured from India. o Geographical Origin:Indian subcontinent (Assam, Bangladesh, India, Nepal and Sri Lanka), Laos and Myanmar.
• Boswellia serrata o Source: This plant is procured from India as well as from abroad. Geographical Origin: Native to much of India and the Punjab region that extends into Pakistan.
• Camellia sinensis o Source: The plant is procured from India. o Geographical Origin: Native to East Asia, the Indian Subcontinent, and Southeast Asia.
• Cinnamomum zeylanicum o Source: The plant is procured from Sri Lanka. o Geographical origin :Native to Sri Lanka.
• Curcuma longa o Source: The plant is sourced from India. o Geographical origin:Native to the Indian subcontinent and Southeast Asia. Elettaria cardamomum o Source: The plant is sourced from India. o Geographical origin :Native to Southern India
• Nigella sativa o Source: The plant is procured from India. o Geographical origin: Native to a large region of the eastern Mediterranean, northern Africa, the Indian subcontinent, and West Asia.
• Piper longum o Source: The plant is procured from India. o Geographical origin :Native of the Indo-Malaya region
• Piper nigrum o Source: The plant is procured from India. o Geographical origin: Native to present-day South India and is extensively cultivated in tropical regions.Vietnam is the largest producer and exporter of pepper.
• Plumbago zeylanica o Source: The plant is procured from India and Sri Lanka. o Geographical origin:Native to Southeast Asia, Indonesia, the Philippines, and Yunnan in southern China.
• Solanum xanthocarpum o Source: The plant is procured from India. o Geographical origin: This plant is cultivated in Himalayas, South- East Malaysia, Australia, and Polynesia region.
• Syzygium aromaticum o Source: The plant is procured from abroad and India. o Geographical origin :Native to the Maluku Islands (or Moluccas) in Indonesia.
• Tinospora cordifolia o Source: The plant is procured from India. o Geographical origin: Indigenous to tropical regions of the Indian subcontinent.
• Withanici somnifera o Source: The plant is sourced from India. o Geographical origin: Grows in India, the Middle East, and parts of Africa.
• Zingiber officinale o Source: The plant is sourced fromi ndia. o Geographical origin: Originated in Maritime Southeast Asia and was likely domesticated first by the Austronesian peoples. It was transported with them throughout the Indo-Pacific during the Austronesian expansion (c. 5,000 BP), reaching as far as Hawaii.
In an embodiment, the present invention relates to a poly-herbal composition comprising; a) an extract of Acacia arabica bark in an amount of 15-30% w/w of the composition; b) an extract of Achyranthes aspera root in an amount of 19-28%w/w of the composition; c) an extract of Adhatoda vasica leaf in an amount of 24-27%w/wof the composition; d) an extract of Boswellia serratarcsin in an amount of 25-30%w/w of the composition; e) an extract of Camellia sinensis leaf in an amount of 10-18%w/w of the composition; f) an extract of Cinnamomum zeylanicum bark in an amount of 15-25%w/w of the composition; g) an extract of Curcuma longa rhizome in an amount of 15-18%w/w of the composition; h) an extract of Elettaria cardamomum fruit in an amount of 12-14%w/w of the composition; i) an extract of Nigella sativasccA in an amount ofl8-20%w/w of the composition; j) an extract of Piper longum fruit in an amount of 22-25%w/w of the composition; k) an extract of Piper nigrum fruit in an amount of 20-22%w/w of the composition; l) an extract of Plumbago zeylanica root in an amount of 10-20%w/w of the composition; m) an extract of Solanum xanthocarpum fruit in an amount of 18-22%w/w of the composition; n) an extract of Syzygium aromaticum bud in an amount ofl0-19%w/w of the composition; o) an extract of Tinospora cordifolia aerial part in an amount of 14-24% w/w of the composition; p) an extract of Withania somnifera rhizome in an amount of 15-23% w/w of the composition; and q) an extract of Zingiber officinale rhizome in an amount of 14-26%w/w of the composition.
The poly-herbal composition of the present invention may contain the additive s/excipients selected from permitted fillers, stabilizer, lubricants, preservative, moisture absorbents, binders, disintegrating agents, colouring agents, flavouring agents in suitable amounts depending on solid and liquid dosage forms.
In an embodiment, the parts of the herbs/plants used in said composition are: a) Acacia arabica: Bark b) Achyranthes aspera: Root and seed c) Adhatoda vasica: Leaves d) Boswellia serrata: Resin e) Camellia sinensis: Green leaves f) Cinnamomum zeylanicum: Bark g) Curcuma longa: Rhizome h) Elettaria cardamomum: Fruit i) Nigella sativa: Seed j) Piper longum: Fruit k) Piper nigrum: Fruit l) Plumbago zeylanica: Root m) Solanum xanthocarpum: Fruit n) Syzygium aromaticum: Bud o) Tinospora cordifolia: Aerial portion p) Withania somnifera: Rhizome q) Zingiber officinale: Rhizome
In another embodiment, the present invention discloses the process for preparation of said poly-herbal composition comprising; i. Extracting the plant materials of Acacia arabica, Achyranthes aspera, Adhatoda vasica, Boswellia serrata, Camellia sinensis, Plumbago zeylanica, Solanum xanthocarpum, Tinospora cordifolia, Withania somnifera collectively or individually with water in the ratio of 1:4 to 1:8 followed by subjecting to a hydroalcoholic extraction in the ratio between 1:2 and 1:6 and standardizing the phytoconstituents to 30-40% solids by concentration, followed by spray drying to uniformity; ii. Individually extracting 50% percent of the amount of
Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinale using the solvent based on the characteristics of the respective plant material followed by stripping off the excess solvent and standardizing the oleoresins derived from said plants; iii. Encapsulating the oleoresins of step (ii) with a natural polymer; iv. Subjecting the remaining 50% of the plant material of
Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinale to hydro-alcoholic extraction followed by spray drying; v. Blending the spray dried material of step (i) and (iv) with encapsulated extracts of step (iii) in appropriate proportion to homogeneity, adding acceptable additive s/excipients to obtain the desired composition.
Accordingly, the bark of Acacia arabica, the seeds of Achyranthes aspera, the leaves of Adhatoda vasica, the resin of Boswellia serrata, the green leaves of Camellia sinensis, the root of Plumbago zeylanica, the fruit of Solanum xanthocarpum, the aerial portion of Tinospora cordifolia, the rhizome of Withania somnifera are subjected to extraction collectively or individually with water in the ratio of 1:4 to 1:8. This is followed by extraction in hydro-alcoholic mixture in the ratio between 1:2 and 1:6 wherein the important phytoconstituents such as alkaloids, flavonoids, glycosides and saponins, and active compounds such as catechins, tannic acid, vasicine, withanolide, piperine, curcuminoids, eugenol and gingerols,are extracted and standardizedto 30-40% solids by concentration, followed by spray drying to uniformity.
As in step (ii), 50% of the total plant material of the bark of Cinnamomum zeylanicum, the rhizome of Curcuma longa, the fruit of Elettaria cardamomum, the seed of Nigella sativa, the fruit of Piper longum, the fruit of Piper nigrum, the bud of Syzygium aromaticum and the rhizome of Zingiber officinale are subjected to individual extraction with suitable solvents which are standardized to the active oleoresins or its analogues derived from said plants followed by stripping off the solvent from the extract.
The standardized oleoresins obtained were then encapsulated with the natural polymer, gum acacia, for further formulation processing. The remaining 50% of the total plant material of the bark of Cinnamomum zeylanicum, the rhizome of Curcuma longa, the fruit of Elettaria cardamomum, the seed of Nigella sativa, the fruit of Piper longum, the fruit of Piper nigrum, the bud of Syzygium aromaticum and the rhizome of Zingiber officinale are subjected to hydro-alcoholic extraction and collectively spray dried.
All the spray dried extracts and encapsulated extracts were blended to homogeneity and granulated (to avoid addition of preservatives) or used as such along with permitted fdlers, preservatives, moisture absorbents, stabilizers, lubricants, binders colouring agents, flavouring agents and such acceptable inactive compounds to formulate the desired composition.
The extractions may be carried out through aqueous solvent or organic solvent, not restricted to ethanol, methanol, ethyl acetate, acetone, ethylene chloride or as per the need of the extractable active compounds from individual plant materials.
Typically, the particle size of the standardized plant extracts used for preparing the poly-herbal composition is less than 100 microns and the moisture content is less than 5%.
In another embodiment, the poly-herbal composition of the present invention may be formulated as nutraceutical composition in solid or liquid form such as dry powder, tablets, capsules, pills, soft gel capsule, lozenges, syrups, suspensions and the like.
In an embodiment, the poly-herbal composition is formulated as capsules which contain the standardized extracts of the plants/herbs at dosages of 260-400mg per capsule.
In another embodiment, the dosage of the standardized extracts of the plants/herbs in tablets or in lozenges, as powders, pills, syrups, suspensions and the like depend on a number of factors including whether the extracts of the plants/herbs as active is to be administered for therapeutic use, the type of viral infection, the severity of the condition, the age of the individual, and related factors including weight and general health of the individual as may be determined in accordance with accepted medical principles. Similarly, frequency of administration of the poly-herbal composition can be determined by continuously monitoring the individual's response between each dosage and if necessary, increasing the frequency of administration or alternatively, reducing the frequency of administration.
In an embodiment, the poly-herbal composition of the present invention exhibits immune -modulator activity and can be used for treating the bronchial hyper responsiveness of the lungs when exposed to living and non-living allergens, to relieve fatigue and improving lung function.
In yet another embodiment, the poly-herbal composition of the present invention is effective in treating the hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs.
In another embodiment, the present invention discloses a method for treating the bronchial hyper responsiveness of the lungs when exposed to living and nonliving allergens, to relieve fatigue and improving lung function comprising providing the poly-herbal composition to a subject in need thereof.
In another embodiment, the present invention discloses a method treating the hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs comprising providing the poly-herbal composition to a subject in need thereof.
The present poly-herbal composition addresses the problems related to various respiratory ailments/diseases caused due to living and non-living allergens by controlling and reducing the parameters such as CRP, ESR, IL-6, D-Dimer, LDH and co-morbid conditions which are critical for treating the bronchial hyper responsiveness of the lungs, to relieve fatigue and improving lung function. The poly-herbal composition of the present invention is useful for regulating the expression of cytokines from triggered immune cells thereby controlling the extraordinary response, repairing the lungs and helping restore lung function.
EXPERIMENTAL
• Example 1: Poly-herbal Composition
Figure imgf000015_0001
Example 2: Process for the preparation of poly-herbal Composition
(i) The bark of Acacia arabica (110 kg), the seeds of Achyranthes aspera (150 kg), the leaves of Adhatoda vasica (360 kg), the resin of Boswellia serrata (40 Kg), the green leaves of Camellia sinensis (100 kg), the root of Plumbago zeylanica (42 kg), the fruit of Solanum xanthocarpum (110 kg), the aerial portion of Tinospora cordifolia (50 kg), the rhizome of Withania somnifera (40 kg) were pulverized to coarse powder and extracted collectively or individually with water in the ratio of 1:4 to 1:8 for 6 to 8 hrs at 70°C. This was followed by extraction in a hydro-alcoholic mixture in a ratio between 1:2 and 1:6 for 12 to 15 hrs at 60°C wherein the important phytoconstituents such as catechins, tannic acid, vasicine, withanolide, piperine, curcuminoids, eugenol and gingerols were extracted and standardizedto 30-40% solids by concentration, followed by spray drying to homogeneity.
(ii) The bark of Cinnamomum zeylanicum(30 kg), the rhizome of Curcuma longa (40 kg), the fruit of Elettaria cardamomum (2 kg), the seed of Nigella sativa (50 kg), the fruit of Piper longum (30 kg), the fruit of Piper nigrum(75 kg), the bud of Syzygium aromaticum(6Q kg) and the rhizome of Zingiber officinale(6Q kg) were pulverized to a coarse powder. 50% of eachplant material viz. Cinnamomum zeylanicum(15 kg) was extracted using acetone for 12hrs at 40°C.The rhizome of Curcuma longa(2() kg) was extracted using the solvent mixture of ethyl acetate and hexane for 12hrs at 60°C. The fruit of Elettaria cardamomum (1 kg) was extracted by steam distillation (100°C) for extracting oil and in ethyl acetate for 12hrs at 40°C. The seed of Nigella sativa(25\sg) was subjected to supercritical fluid extraction for 8hrs at 30°C. The fruit of Piper longum( \5 kg) was extracted using the solvent mixture of acetone and ethyl acetate for 12hrs at 60°C. The fruit of Piper nigrum (37.5 kg) was extracted using ethyl acetate for 12hrs at 60°C. The bud of Syzygium aromaticum (30 kg) was extracted using the solvent mixture of ethyl acetate and hexane for 12hrs at 40°C. The rhizome of Zingiber officinale( Q kg) was extracted using the solvent mixture of ethyl acetate and acetone for 12hrs at 40°C.
The extracts were standardized to 6-7% of active oleoresins or its analogues derived from said plants followed by stripping off the solvent under vacuum from the extract.
The standardized oleoresins so obtained were then encapsulated with the natural polymer, gum acacia for further formulation process.
(iii) The remaining 50% of the total plant material of the bark of Cinnamomum zeylanicum, the rhizome of Curcuma longa, the fruit of Elettaria cardamomum, the seed of Nigella sativa, the fruit of Piper longum, the fruit of Piper nigrum, the bud of Syzygium aromaticum and the rhizome of Zingiber officinaleoi step (ii) were subjected to hydro-alcoholic (30:70) extraction and collectively spray dried.
(iv) All the spray dried extracts of step (i) and (iii) and encapsulated extracts of step (ii) were blended to homogeneity, added permitted fdlers, preservatives, moisture absorbents and pharmaceutically inactive compounds to formulate the desired composition in solid and liquid forms.
Example 3: Capsule composition
Figure imgf000017_0001
Figure imgf000018_0001
Example 4: Efficacy study of the poly-herbal composition of the present invention
The fine blend of the standardized extracts of example 3was filled into capsules to give oral dosage of 2 capsules of approximately400 mg each, i.e., 2-0-2 for treatment of patients suffering from respiratory illnesses and who were positive to viral RNA with or without lung involvement as measured through HRCT (High- resolution computed tomography) scan.
A study was performed to elucidate the effect of the invention in patients with respiratory conditions, including those positive for SARS-CoV-2 virus (COVID- 19). Mild oxygen requirements (up to 5L/min) or the presence of co-morbid conditions, such as Type 2 diabetes or hypertension, did not deter patients from enrollment and only severely affected individuals who required ventilator support were excluded from the analysis.
A total of 43 volunteers (both male and female) were enrolled. The parameters studied include complete blood cell counts, Liver Function tests, Kidney function tests, HRCT scan, IL-6, LDH, D-Dimer, CRP and external symptoms such as cough, fever, respiration rate and oxygen requirements.
The volunteers were classified into mild and moderately affected based on their lung involvement and blood markers such as IL-6, LDH, D-Dimer and CRP. The volunteers’ data was further classified on the basis of age, co-morbidities, abnormal levels of blood parameters, and symptoms such as cough, fever and oxygen requirement etc. and analyzed. Results:
Out of 43 volunteers recruited, 23 volunteers were taken for analysis as they had a minimum of 2 data points, one before taking the present polyherbal composition and another taken after completion of the course. There were 16 patients in the mild category and 7 patients in the moderate category, classified based on their CT scores, D-Dimer, CRP and IL-6 values, and co-morbid conditions.
Moderately affected patients had abnormal values of a few blood cell counts, such as RBC, leucocytes (WBC), platelets, neutrophils, eosinophils and lymphocytes, along with enhanced values of CRP, IL-6, D-Dimer, LDH and Ferritin. Mild patients had less than 5% of lung involvement of the disease whereas moderately affected patients had up to 45% of lung involvement with respect to their HRCT images.
D-Dimer
D-dimer is a protein fragment (small piece) that is made when a blood clot dissolves in the body. A decrease in D-Dimer levels was observed after taking the poly-herbal composition of the present invention thereby restoring normalcy. At the initial stage the D-Dimer levels in the volunteers were higher than the normal maximum limit. Upon taking the poly-herbal composition, the D-Dimer levels tapered off until they were within the acceptable range (Figs. 1(a) and (b)).
CRP
C-Reactive protein (CRP) is a protein made by the liver. CRP levels in the blood increase when there is a condition causing inflammation in the body. A CRP test measures the amount of CRP in the blood, to detect inflammation due to acute conditions or to monitor the severity of disease in chronic conditions. A decrease in C - reactive protein levels after taking the poly-herbal composition was observed, restoring normalcy in volunteers after 5 days. In the initial stage the CRP levels in the volunteers were higher than the normal range. Increase in CRP levels can be attributed to the progression of the disease (Figs 2(a) and (b)).
IL-6
Several studies have pointed out that Interleukin-6 (IL-6) seems to be associated with an inflammatory response, respiratory failure, need for mechanical ventilation and/or intubation, and mortality. Volunteers with the highest levels of complications exhibited 3 or more times higher levels ofIL-6 than noncomplicated volunteers. IL-6 is predictive of progression in severity of the disease and in-hospital mortality. A decrease in IL-6 levels after taking the poly herbal composition was observed, restoring to normalcy levels of <7pg/ml (Fig 3).
Leukocyte
A decreased leukocyte count (less than 4000 cells/mm) in the early stages of infection of the virus and from 3rd day after the consumption of poly-herbal composition was noted. The volunteers showed increased counts (indicative of an increased response to the virus) and with a maximum value between 6500 and 7280 cells(average) on the 5th day (Fig 4).
Apart from the above parameters, there were abnormal values in few of the volunteers in some of the blood cell counts like RBC, neutrophils, eosinophils at the time of admission and all were found to return to normal range within 5 to 7 days of treatment with poly-herbal composition of the present invention.
Complete blood count (stratified by severity of symptoms presented)
Figure imgf000021_0001
Symptomatic Characteristics
Figure imgf000021_0002
Clinical symptoms and pulmonary function parameters were measured in volunteers who showed significant improvement after 8weeks depicted in Table 1 below:
Table 1:
Figure imgf000022_0001
*FEV1 (Forced expiratory volume) is an important measure in evaluating asthmatic and chronic obstructive pulmonary disease (COPD).
*PEFR(Peak expiratory flow) is a person's maximum speed of expiration, as measured with a peak flow meter.
*FVC (forced vital capacity) is used to study obstructive lung diseases. *FEF(Forced expiratory flow) is used to assess peripheral airway function.
The marked improvement with respect to the platelet counts, IL-6 marker, D- Dimer values, leukocyte counts and CRP values within a short period of time indicated that the present poly-herbal composition is efficacious in reducing the hyperinflammatory response of the immune cells. This protects the lungs from catastrophe due to the viral infection and helps in reversing the pneumonic conditions of the lungs. Technical Advancement:
• Though few of the plants used in the present poly-herbal composition viz.
Piper nigrum and Piper longum, Curcuma longa,Achyranthes aspera, Syzygium aromaticum, Acacia arabica, Zingiber officinale, Adhatoda vasica, Solanum xanthocarpum, Elettaria cardamomum are known to have different functions such as protease inhibitor(anti-viral), antiinflammatory, IL-6 blocker, prostaglandin biosynthesis inhibitor, reduction of bronchial mucosal oedema, individually or in combination, the present poly herbal composition provides total relief from all the symptoms in short time as shown above.
• The poly-herbal composition is safe without any side effects with the potential to overcome the limitations of the present synthetic drugs available in the market.
Although the invention has been described in detail in the foregoing for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims.

Claims

We Claim;
1. A poly-herbal composition comprising; a) an extract of Acacia Arabica bark in an amount of 15-30%w/w of the composition; b) an extract of Achyranthes aspera root in an amount of 19-28%w/w of the composition; c) an extract of Adhatoda vasica leaf in an amount of 24-27%w/w of the composition; d) an extract of Boswellia serrata resin in an amount of 25-30%w/w of the composition; e) an extract of Camellia sinensis leaf in an amount of 10-18%w/w of the composition; f) an extract of Cinnamomum zeylanicum bark in an amount of 15- 25%w/w of the composition; g) an extract of Curcuma longa rhizome in an amount of 15-18%w/w of the composition; h) an extract of Elettaria cardamomum fruit in an amount of 12-14%w/w of the composition; i) an extract of Nigella sativa seed in an amount of 18-20%w/w of the composition; j) an extract of Piper longum fruit in an amount of 22-25 %w/w of the composition; k) an extract of Piper nigrum fruit in an amount of 20-22%w/w of the composition; l) an extract of Plumbago zeylanica root in an amount of 10-20%w/w of the composition; m) an extract of Solanum xanthocarpum fruit in an amount of 18-22%w/w of the composition; n) an extract of Syzygium aromaticum bud in an amount ofl0-19%w/w of the composition; o) an extract of Tinospora cordifolia aerial part in an amount of 14- 24% w/w of the composition; p) an extract of Withania somnifera rhizome in an amount of 15-23% w/w of the composition; and q) an extract of Zingiber officinale rhizome in an amount of 14-26%w/w of the composition; wherein the composition contains pharmaceutically acceptable additives/excipients. The poly-herbal composition as claimed in claim 1, wherein the process for preparation comprising; a. Extracting the plant components of Acacia arabica, Achyranthes aspera, Adhatoda vasica, Boswellia serrata, Camellia sinensis, Plumbago zeylanica, Solanum xanthocarpum, Tinospora cordifolia, Withania somnifera collectively or individually with water in the ratio of 1:4 to 1:8 and then subjecting to a hydroalcoholic mixture in the ratio between 1:2 and 1:6 and standardizing the phyto constituents to 30-40% solids by concentration, followed by spray drying to uniformity; b. Individually extracting 50% percent of the amount of Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinale using the solvent based on the characteristics of the respective plant components followed by stripping off the excess solvent and standardizing the oleoresins derived from said plants; c. Encapsulating the oleoresins of step (ii) with a natural polymer; d. Subjecting the remaining 50% of the plant material of
Cinnamomum zeylanicum, Curcuma longa, Elettaria cardamomum, Nigella sativa, Piper longum, Piper nigrum, Syzygium aromaticum and Zingiber officinale to hydro-alcoholic extraction followed by spray drying; e. Blending the spray dried material of step (i) and (iv) with encapsulated extracts of step (iii) in appropriate proportion to homogeneity, adding acceptable additive s/excipients to obtain the desired composition.
3. The poly-herbal composition as claimed in claims 1 and 2, wherein the additives/excipients are selected from permitted fillers, stabilizers, lubricants, preservatives, moisture absorbents, binders, disintegrating agents, colouring agents, flavouring agents and the like in suitable amount.
4. The poly-herbal composition as claimed in claims 1 and 2, wherein the composition is in solid or liquid form such as dry powder, tablets, capsules, pills, soft gel capsule, lozenges, syrups, suspensions and the like.
5. The method of treating hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs comprising providing the poly-herbal composition, as claimed in claim 1, to the subject in need.
6. The method for treating or bronchial hyperresponsiveness of the lungs when exposed to living and non-living allergens, to relieve fatigue and improving lung function comprising providing the poly-herbal composition, as claimed in claim 1, to a subject in need.
7. The poly-herbal composition as claimed in claim 1 for use in treating the hyperinflammatory response of the immune cells and in reversing the pneumonic conditions of the lungs.
8. The poly-herbal composition as claimed in claim 1 for use in treating bronchial hyperresponsiveness of the lungs when exposed to living and non-living allergens, to relieve fatigue and improving lung function.
PCT/IN2023/050636 2022-06-30 2023-06-30 Poly-herbal composition for respiratory illnesses WO2024003946A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2335598A (en) * 1998-03-23 1999-09-29 Dalmia Centre For Biotechnolog A herbal composition
WO2003055558A1 (en) 2001-12-31 2003-07-10 Dalmia Centre For Research And Development Polyherbal composition for the treatment of bronchial asthma and the process
IN201621037854A (en) 2016-11-05 2018-05-25
WO2020208659A1 (en) 2020-04-19 2020-10-15 Rajesh Biswas Anti-viral anti-bacterial immunoboosting composition of herbal extracts in synergistic ratios

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2335598A (en) * 1998-03-23 1999-09-29 Dalmia Centre For Biotechnolog A herbal composition
WO2003055558A1 (en) 2001-12-31 2003-07-10 Dalmia Centre For Research And Development Polyherbal composition for the treatment of bronchial asthma and the process
IN201621037854A (en) 2016-11-05 2018-05-25
WO2020208659A1 (en) 2020-04-19 2020-10-15 Rajesh Biswas Anti-viral anti-bacterial immunoboosting composition of herbal extracts in synergistic ratios

Non-Patent Citations (2)

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Title
MURALI ET AL: "Plant-based formulation in the management of chronic obstructive pulmonary disease: A randomized double-blind study", RESPIRATORY MEDICINE, ELSEVIER, AMSTERDAM, NL, vol. 100, no. 1, 1 January 2006 (2006-01-01), pages 39 - 45, XP005219514, ISSN: 0954-6111, DOI: 10.1016/J.RMED.2005.04.011 *
MURALI P M ET AL: "Plant-based formulation for bronchial asthma: a controlled clinical trial to compare its efficacy with oral salbutamol and theophylline.", RESPIRATION; INTERNATIONAL REVIEW OF THORACIC DISEASES 2006, vol. 73, no. 4, 2006, pages 457 - 463, XP009547981, ISSN: 0025-7931 *

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